J Korean Orthop Assoc.  2007 Oct;42(5):665-670. 10.4055/jkoa.2007.42.5.665.

The Relationships between Homocysteine, Folate, MTHER and TSER Polymorphism for Osteoporotic Compression Fracture in Postmenopausal Women

• Shin DE
• Cho DY
• Yoon HK
• Kim NG
• Lee IS

• KMID: 2186475
• DOI: http://doi.org/10.4055/jkoa.2007.42.5.665

Abstract

PURPOSE: To analyze the relationships between homocysteine, folate, MTHFR and TSER polymorphism for postmenopausal women with osteoporotic compression fractures.
MATERIALS AND METHODS
Forty-three postmenopausal compression fracture patients and as many normal controls were included. The plasma homocysteine and folate levels were measured using a FPIA (fluorescent polarizing immunoassay) kit. The MTHFR and TSER genotypes were amplified by PCR (polymerase chain reaction) and separated by RFLP (restriction fragment length polymorphism) in a 3.5% agarose gel.
RESULTS
The plasma folate level was significantly lower in the postmenopausal women with osteoporotic compression fractures, particularly in the MTHFR 677CT and TSER 2R (-) genotypes. However, the plasma homocysteine level and MTHFR C677T polymorphism were similar to the control group.
CONCLUSION
A low folate level and the TSER 2R (-) genotype can be associated with osteoporotic compression fractures in postmenopausal women.

Keyword

Osteoporotic fracture; Homocysteine; Folate; MTHFR; TSER

MeSH Terms

Female
Folic Acid*
Fractures, Compression*
Genotype
Homocysteine*
Humans
Osteoporotic Fractures
Plasma
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Sepharose
Folic Acid
Homocysteine
Sepharose

Reference

1. Blom HJ, Kleinveld HA, Boers GH, et al. Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinemia. Eur J Clin Invest. 1995. 25:149–154.

2. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999. 353:878–882.

3. Diaz-Arrastia R. Homocysteine and neurologic disease. Arch Neurol. 2000. 57:1422–1427.

4. D'Angelo A, Selhub J. Homocysteine and thrombotic disease. Blood. 1997. 90:1–11.

5. Eichinger S, Strumpflen A, Hirschl M, et al. Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Thromb Haemost. 1998. 80:566–569.

6. Franken DG, Boers GH, Blom HJ, Cruysberg JR, Trijbels FJ, Hamel BC. Prevalence of familial mild hyperhomocysteinemia. Atherosclerosis. 1996. 125:71–80.

7. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995. 10:111–113.

8. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet. 1995. 56:1052–1059.

9. Harmon DL, Doyle RM, Meleady R, et al. Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. Arterioscler Thromb Vasc Biol. 1999. 19:208–211.

10. Horie N, Aiba H, Oguro K, Hojo H, Takeishi K. Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5'-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct. 1995. 20:191–197.

11. Jakubowski H, Zhang L, Bardeguez A, Aviv A. Homocysteine thiolactone and protein homocystinylation in human endothelial cells: implications for atherosclerosis. Circ Res. 2000. 87:45–51.

12. Kang AH, Trelstad RL. A collagen defect in homocystinuria. J Clin Invest. 1973. 2:2571–2578.

13. Kawakami K, Omura K, Kanehira E, Watanabe Y. Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res. 1999. 19:3249–3252.

14. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocysteine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998. 338:1009–1015.

15. Melton LJ 3rd. Adverse outcomes of osteoporotic fractures in the general population. J Bone Miner Res. 2003. 18:1139–1141.

16. Olszewski AJ, McCully KS. Homocysteine metabolism and the oxidative modification of proteins and lipids. Free Rad Biol Med. 1993. 14:683–693.

17. Ray NF, Chan JK, Thamer M, Melton LJ 3rd. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res. 1997. 12:24–35.

18. Selhub J, Jacques PF, Bostom AG, et al. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med. 1995. 332:286–291.

19. Selhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr. 1992. 55:131–138.

20. Trinh BN, Ong CN, Coetzee GA, Yu MC, Laird PW. Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels. Hum Genet. 2002. 111:299–302.

21. Tucker KL, Mahnken B, Wilson PW, Jacques P, Selhup J. Folic acid fortification of the food supply. Potential benefits and risks for the elderly population. JAMA. 1996. 276:1879–1885.

22. van der Put NM, Gabreëls F, Stevens EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998. 62:1044–1051.

23. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004. 350:2033–2041.